Journal
STEM CELL REPORTS
Volume 3, Issue 5, Pages 858-875Publisher
CELL PRESS
DOI: 10.1016/j.stemcr.2014.08.012
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Funding
- BioRN Spitzencluster ''Molecular and Cell Based Medicine''
- German Bundesministerium fur Bildung und Forschung
- Sonderforschungsbereich [SFB873]
- Deutsche Forschungsgemeinschaft
- Dietmar Hopp Foundation
- European Community's Seventh Framework Programme (FP7)
- RADIANT [305626]
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Hematopoietic stem cells possess lifelong self-renewal activity and generate multipotent progenitors that differentiate into lineage-committed and subsequently mature cells. We present a comparative transcriptome analysis of ex vivo isolated mouse multipotent hematopoietic stem/progenitor cells (Lin(neg)SCA-1 (+)c-KIT+) and myeloid committed precursors (Lin(neg)SCA-1(neg)c-KIT+). Our data display dynamic transcriptional networks and identify a stem/progenitor gene expression pattern that is characterized by cell adhesion and immune response components including kallikrein-related proteases. We identify 498 expressed lncRNAs, which are potential regulators of multipotency or lineage commitment. By integrating these transcriptome with our recently reported proteome data, we found evidence for posttranscriptional regulation of processes including metabolism and response to oxidative stress. Finally, our study identifies a high number of genes with transcript isoform regulation upon lineage commitment. This in-depth molecular analysis outlines the enormous complexity of expressed coding and noncoding RNAs and posttranscriptional regulation during the early differentiation steps of hematopoietic stem cells toward the myeloid lineage.
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